Engaging adolescents in changing behaviour (EACH-B): a study protocol for a cluster randomised controlled trial to improve dietary quality and physical activity.

BACKGROUND: Poor diet and lack of physical activity are strongly linked to non-communicable disease risk, but modifying them is challenging. There is increasing recognition that adolescence is an important time to intervene; habits formed during this period tend to last, and physical and psychological changes during adolescence make it an important time to help individuals form healthier habits. Improving adolescents' health behaviours is important not only for their own health now and in adulthood, but also for the health of any future children. Building on LifeLab-an existing, purpose-built educational facility at the University of Southampton-we have developed a multi-component intervention for secondary school students called Engaging Adolescents in Changing Behaviour (EACH-B) that aims to motivate and support adolescents to eat better and be more physically active. METHODS: A cluster randomised controlled trial is being conducted to evaluate the effectiveness of the EACH-B intervention. The primary outcomes of the intervention are self-reported dietary quality and objectively measured physical activity (PA) levels, both assessed at baseline and at 12-month follow-up. The EACH-B intervention consists of three linked elements: professional development for teachers including training in communication skills to support health behaviour change; the LifeLab educational module comprising in-school teaching of nine science lessons linked to the English National Curriculum and a practical day visit to the LifeLab facility; and a personalised digital intervention that involves social support and game features that promote eating better and being more active. Both the taught module and the LifeLab day are designed with a focus on the science behind the messages about positive health behaviours, such as diet and PA, for the adolescents now, in adulthood and their future offspring, with the aim of promoting personal plans for change. The EACH-B research trial aims to recruit approximately 2300 secondary school students aged 12-13 years from 50 schools (the clusters) from Hampshire and neighbouring counties. Participating schools will be randomised to either the control or intervention arm. The intervention will be run during two academic years, with continual recruitment of schools throughout the school year until the sample size is reached. The schools allocated to the control arm will receive normal schooling but will be offered the intervention after data collection for the trial is complete. An economic model will be developed to assess the cost-effectiveness of the EACH-B intervention compared with usual schooling. DISCUSSION: Adolescents' health needs are often ignored and they can be difficult to engage in behaviour change. Building a cheap, sustainable way of engaging them in making healthier choices will benefit their long-term health and that of their future children. TRIAL REGISTRATION: ISRCTN 74109264 . Registered on 30 August 2019. EACH-B is a cluster randomised controlled trial, funded by the National Institute for Health Research (RP-PG-0216-20004).

Fulvestrant for Untreated Hormone-Receptor Positive Locally Advanced or Metastatic Breast Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Clinical and cost-effectiveness evidence on fulvestrant for untreated hormone-receptor positive locally advanced or metastatic breast cancer was submitted to the single technology appraisal process of the National Institute for Health and Care Excellence by the manufacturer of fulvestrant. The Southampton Health Technology Assessments Centre was commissioned by the National Institute for Health and Care Excellence as an independent Evidence Review Group to critique the company's submitted evidence. Fulvestrant was compared directly with anastrozole in two randomised controlled trials and was compared indirectly by means of a network meta-analysis with anastrozole, letrozole and tamoxifen. This article summarises the Evidence Review Group's review of the company's submission and summarises the guidance the National Institute for Health and Care Excellence Appraisal Committee issued in January 2018. The Evidence Review Group had several concerns, the most important of which related to the degree to which fulvestrant might confer a benefit in overall survival. This was because mature data were not available from the key phase III trial FALCON. The economic model was sensitive to changes in overall survival and the Evidence Review Group considered the incremental cost-effectiveness ratio was uncertain and likely to increase once mature results from FALCON become available. The National Institute for Health and Care Excellence Appraisal Committee concluded that fulvestrant could not be recommended for treating locally advanced or metastatic estrogen-receptor-positive breast cancer in postmenopausal women who have not received previous endocrine therapy.

Accuracy of fundus autofluorescence imaging for the diagnosis and monitoring of retinal conditions: a systematic review.

BACKGROUND: Natural fluorescence in the eye may be increased or decreased by diseases that affect the retina. Imaging methods based on confocal scanning laser ophthalmoscopy (cSLO) can detect this 'fundus autofluorescence' (FAF) by illuminating the retina using a specific light 'excitation wavelength'. FAF imaging could assist the diagnosis or monitoring of retinal conditions. However, the accuracy of the method for diagnosis or monitoring is unclear. OBJECTIVE: To conduct a systematic review to determine the accuracy of FAF imaging using cSLO for the diagnosis or monitoring of retinal conditions, including monitoring of response to therapy. DATA SOURCES: Electronic bibliographic databases; scrutiny of reference lists of included studies and relevant systematic reviews; and searches of internet pages of relevant organisations, meetings and trial registries. Databases included MEDLINE, EMBASE, The Cochrane Library, Web of Science and the Medion database of diagnostic accuracy studies. Searches covered 1990 to November 2014 and were limited to the English language. REVIEW METHODS: References were screened for relevance using prespecified inclusion criteria to capture a broad range of retinal conditions. Two reviewers assessed titles and abstracts independently. Full-text versions of relevant records were retrieved and screened by one reviewer and checked by a second. Data were extracted and critically appraised using the Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS) for assessing risk of bias in test accuracy studies by one reviewer and checked by a second. At all stages any reviewer disagreement was resolved through discussion or arbitration by a third reviewer. RESULTS: Eight primary research studies have investigated the diagnostic accuracy of FAF imaging in retinal conditions: choroidal neovascularisation (one study), reticular pseudodrusen (three studies), cystoid macular oedema (two studies) and diabetic macular oedema (two studies). Sensitivity of FAF imaging using an excitation wavelength of 488 nm was generally high (range 81-100%), but was lower (55% and 32%) in two studies using longer excitation wavelengths (514 nm and 790 nm, respectively). Specificity ranged from 34% to 100%. However, owing to limitations of the data, none of the studies provide conclusive evidence of the diagnostic accuracy of FAF imaging. LIMITATIONS: No studies on the accuracy of FAF imaging for monitoring the progression of retinal conditions or response to therapy were identified. Owing to study heterogeneity, pooling of diagnostic outcomes in meta-analysis was not conducted. All included studies had high risk of bias. In most studies the patient spectrum was not reflective of those who would present in clinical practice and no studies adequately reported how FAF images were interpreted. CONCLUSIONS: Although already in use in clinical practice, it is unclear whether or not FAF imaging is accurate, and whether or not it is applied and interpreted consistently for the diagnosis and/or monitoring of retinal conditions. Well-designed prospective primary research studies, which conform to the paradigm of diagnostic test accuracy assessment, are required to investigate the accuracy of FAF imaging in diagnosis and monitoring of inherited retinal dystrophies, early age-related macular degeneration, geographic atrophy and central serous chorioretinopathy. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014014997. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Educational interventions to improve quality of life in people with chronic inflammatory skin diseases: systematic reviews of clinical effectiveness and cost-effectiveness.

BACKGROUND: Inflammatory skin diseases include a broad range of disorders. For some people, these conditions lead to psychological comorbidities and reduced quality of life (QoL). Patient education is recommended in the management of these conditions and may improve QoL. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of educational interventions to improve health-related quality of life (HRQoL) in people with chronic inflammatory skin diseases. DATA SOURCES: Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched to July 2014. Bibliographies of retrieved papers were searched and an Advisory Group contacted. REVIEW METHODS: Systematic reviews were conducted following standard methodologies. Clinical effectiveness studies were included if they were undertaken in people with a chronic inflammatory skin condition. Educational interventions that aimed to, or could, improve HRQoL were eligible. Studies were required to measure HRQoL, and other outcomes such as disease severity were also included. Randomised controlled trials (RCTs) or controlled clinical trials were eligible. For the review of cost-effectiveness, studies were eligible if they were full economic evaluations, cost-consequence or cost analyses. RESULTS: Seven RCTs were included in the review of clinical effectiveness. Two RCTs focused on children with eczema and their carers. Five RCTs were in adults. Of these, two were of people with psoriasis, one was of people with acne and two were of people with a range of conditions. There were few similarities in the interventions (e.g. the delivery mode, the topics covered, the duration of the education), which precluded any quantitative synthesis. Follow-up ranged from 4 weeks to 12 months, samples sizes were generally small and, overall, the study quality was poor. There appeared to be positive effects on HRQoL in participants with psoriasis in one trial, but no difference between groups in another trial in which participants had less severe psoriasis. Carers of children in one RCT of eczema showed improvement in HRQoL; however, in a RCT evaluating a website intervention there were no demonstrable effects on HRQoL. Neither the RCT in those adults with acne nor the RCT in those adults with mixed skin conditions demonstrated an effect on HRQoL. One RCT reported subgroups with atopic dermatitis or psoriasis and education was effective for psoriasis only. Other outcomes also showed mixed results. It is unclear how clinically meaningful any of the observed improvements are. Three studies of cost-effectiveness were included. The interventions, comparators and populations varied across the studies and, overall, the studies provided limited information on cost-effectiveness. The studies did provide detailed information on resources and costs that could be useful to inform a future cost-effectiveness evaluation in this area. LIMITATIONS: The application of the inclusion criterion around whether the interventions were aimed at improving HRQoL or the inference that they could improve HRQoL was difficult as information was rarely reported. CONCLUSIONS: There is uncertainty regarding whether educational interventions addressing issues that could improve HRQoL in people with chronic skin conditions are effective. Tentative conclusions about the best approach to delivering these kinds of interventions are that face-to-face, group, sessions may be beneficial; however, text messages may also be effective. Delivery over a period of time and by a multidisciplinary team may also be associated with positive outcomes. There is uncertainty over whether or not educational interventions are cost-effective. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014007426. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The INTRABEAM® Photon Radiotherapy System for the adjuvant treatment of early breast cancer: a systematic review and economic evaluation.

BACKGROUND: Initial treatment for early breast cancer is usually either breast-conserving surgery (BCS) or mastectomy. After BCS, whole-breast external beam radiotherapy (WB-EBRT) is the standard of care. A potential alternative to post-operative WB-EBRT is intraoperative radiation therapy delivered by the INTRABEAM(®) Photon Radiotherapy System (Carl Zeiss, Oberkochen, Germany) to the tissue adjacent to the resection cavity at the time of surgery. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of INTRABEAM for the adjuvant treatment of early breast cancer during surgical removal of the tumour. DATA SOURCES: Electronic bibliographic databases, including MEDLINE, EMBASE and The Cochrane Library, were searched from inception to March 2014 for English-language articles. Bibliographies of articles, systematic reviews, clinical guidelines and the manufacturer's submission were also searched. The advisory group was contacted to identify additional evidence. METHODS: Systematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were conducted. Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to full texts of retrieved papers by one reviewer and checked by a second reviewer. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, and differences in opinion were resolved through discussion at each stage. Clinical effectiveness studies were included if they were carried out in patients with early operable breast cancer. The intervention was the INTRABEAM system, which was compared with WB-EBRT, and study designs were randomised controlled trials (RCTs). Controlled clinical trials could be considered if data from available RCTs were incomplete (e.g. absence of data on outcomes of interest). A cost-utility decision-analytic model was developed to estimate the costs, benefits and cost-effectiveness of INTRABEAM compared with WB-EBRT for early operable breast cancer. RESULTS: One non-inferiority RCT, TARGeted Intraoperative radioTherapy Alone (TARGIT-A), met the inclusion criteria for the review. The review found that local recurrence was slightly higher following INTRABEAM than WB-EBRT, but the difference did not exceed the 2.5% non-inferiority margin providing INTRABEAM was given at the same time as BCS. Overall survival was similar with both treatments. Statistically significant differences in complications were found for the occurrence of wound seroma requiring more than three aspirations (more frequent in the INTRABEAM group) and for a Radiation Therapy Oncology Group toxicity score of grade 3 or 4 (less frequent in the INTRABEAM group). Cost-effectiveness base-case analysis indicates that INTRABEAM is less expensive but also less effective than WB-EBRT because it is associated with lower total costs but fewer total quality-adjusted life-years gained. However, sensitivity analyses identified four model parameters that can cause a switch in the treatment option that is considered cost-effective. LIMITATIONS: The base-case result from the model is subject to uncertainty because the disease progression parameters are largely drawn from the single available RCT. The RCT median follow-up of 2 years 5 months may be inadequate, particularly as the number of participants with local recurrence is low. The model is particularly sensitive to this parameter. CONCLUSIONS AND IMPLICATIONS: A significant investment in INTRABEAM equipment and staff training (clinical and non-clinical) would be required to make this technology available across the NHS. Longer-term follow-up data from the TARGIT-A trial and analysis of registry data are required as results are currently based on a small number of events and economic modelling results are uncertain. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006720. FUNDING: The National Institute for Health Research Health Technology Assessment programme. Note that the economic model associated with this document is protected by intellectual property rights, which are owned by the University of Southampton. Anyone wishing to modify, adapt, translate, reverse engineer, decompile, dismantle or create derivative work based on the economic model must first seek the agreement of the property owners.