The analysis quantifies the enormity of the clinical and economic burdens of NAFLD, which will likely increase as the incidence of NAFLD continues to rise. (Hepatology 2016;64:1577-1586).

Word count: 4222 3 RESEARCH IN CONTEXT Evidence before this studyIt is widely accepted that COPD is substantially under-diagnosed worldwide. Mass population screening with spirometry is not recommended although early identification of undiagnosed patients with clinical disease is generally supported because COPD has significant patient, healthcare and societal burden which could potentially be lessened through timely diagnosis. A comprehensive systematic review of the effectiveness of case-finding studies, published in 2015, revealed 39 published studies but few included a comparator arm. Only one RCT has compared a case-finding approach with routine care to identify clinically significant COPD, identifying that opportunistic administration of a screening questionnaire at practice visits was twice as effective as routine care, but non-comparative studies suggest that high yields could be achieved from active case finding with mailed questionnaires to high risk patients. No previous trial has compared the clinical and costeffectiveness of alternative approaches to case-finding in a real-life primary care setting. Added value of this studyTargetCOPD is the first randomised controlled trial to evaluate the effectiveness and costeffectiveness of active case-finding for COPD compared with opportunistic case finding and to compare these approaches with routine care. Among 54 general practices, we found that when targeting ever smokers aged 40-79 years, active case finding was more than twice as effective as opportunistic case finding, and that together, these targeted approaches were over seven times as effective as current routine care. Active case finding was also more cost-effective than opportunistic case finding. Implications of all the available evidenceIn a real-life setting, active case-finding comprising an initial mailed questionnaire followed by spirometry should be recommended for identifying undiagnosed COPD in primary care. An important proportion of these previously undiagnosed patients have significant breathlessness and earlier identification and management with effective treatments including inhalers and pulmonary rehabilitation has the potential to improve their health. This trial provides the evidence for guidelines which was previously lacking. 4 SUMMARY Background

BackgroundSelf-management (SM) support for patients with chronic obstructive pulmonary disease (COPD) is variable in its coverage, content, method and timing of delivery. There is insufficient evidence for which SM interventions are the most effective and cost-effective.ObjectivesTo undertake (1) a systematic review of the evidence for the effectiveness of SM interventions commencing within 6 weeks of hospital discharge for an exacerbation for COPD (review 1); (2) a systematic review of the qualitative evidence about patient satisfaction, acceptance and barriers to SM interventions (review 2); (3) a systematic review of the cost-effectiveness of SM support interventions within 6 weeks of hospital discharge for an exacerbation of COPD (review 3); (4) a cost-effectiveness analysis and economic model of post-exacerbation SM support compared with usual care (UC) (economic model); and (5) a wider systematic review of the evidence of the effectiveness of SM support, including interventions (such as pulmonary rehabilitation) in which there are significant components of SM, to identify which components are the most important in reducing exacerbations, hospital admissions/readmissions and improving quality of life (review 4).MethodsThe following electronic databases were searched from inception to May 2012: MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Science Citation Index [Institute of Scientific Information (ISI)]. Subject-specific databases were also searched: PEDro physiotherapy evidence database, PsycINFO and the Cochrane Airways Group Register of Trials. Ongoing studies were sourced through themetaRegister of Current Controlled Trials, International Standard Randomised Controlled Trial Number database, World Health Organization International Clinical Trials Registry Platform Portal and ClinicalTrials.gov. Specialist abstract and conference proceedings were sourced through ISI’s Conference Proceedings Citation Index and British Library’s Electronic Table of Contents (Zetoc). Hand-searching through European Respiratory Society, the American Thoracic Society and British Thoracic Society conference proceedings from 2010 to 2012 was also undertaken, and selected websites were also examined. Title, abstracts and full texts of potentially relevant studies were scanned by two independent reviewers. Primary studies were included if ≈90% of the population had COPD, the majority were of at least moderate severity and reported on any intervention that included a SM component or package. Accepted study designs and outcomes differed between the reviews. Risk of bias for randomised controlled trials (RCTs) was assessed using the Cochrane tool. Random-effects meta-analysis was used to combine studies where appropriate. A Markov model, taking a 30-year time horizon, compared a SM intervention immediately following a hospital admission for an acute exacerbation with UC. Incremental costs and quality-adjusted life-years were calculated, with sensitivity analyses.ResultsFrom 13,355 abstracts, 10 RCTs were included for review 1, one study each for reviews 2 and 3, and 174 RCTs for review 4. Available studies were heterogeneous and many were of poor quality. Meta-analysis identified no evidence of benefit of post-discharge SM support on admissions [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.52 to 1.17], mortality (HR 1.07, 95% CI 0.74 to 1.54) and most other health outcomes. A modest improvement in health-related quality of life (HRQoL) was identified but this was possibly biased due to high loss to follow-up. The economic model was speculative due to uncertainty in impact on readmissions. Compared with UC, post-discharge SM support (delivered within 6 weeks of discharge) was more costly and resulted in better outcomes (£683 cost difference and 0.0831 QALY gain). Studies assessing the effect of individual components were few but only exercise significantly improved HRQoL (3-month St George’s Respiratory Questionnaire 4.87, 95% CI 3.96 to 5.79). Multicomponent interventions produced an improved HRQoL compared with UC (mean difference 6.50, 95% CI 3.62 to 9.39, at 3 months). Results were consistent with a potential reduction in admissions. Interventions with more enhanced care from health-care professionals improved HRQoL and reduced admissions at 1-year follow-up. Interventions that included supervised or unsupervised structured exercise resulted in significant and clinically important improvements in HRQoL up to 6 months.LimitationsThis review was based on a comprehensive search strategy that should have identified most of the relevant studies. The main limitations result from the heterogeneity of studies available and widespread problems with their design and reporting.ConclusionsThere was little evidence of benefit of providing SM support to patients shortly after discharge from hospital, although effects observed were consistent with possible improvement in HRQoL and reduction in hospital admissions. It was not easy to tease out the most effective components of SM support packages, although interventions containing exercise seemed the most effective. Future work should include qualitative studies to explore barriers and facilitators to SM post exacerbation and novel approaches to affect behaviour change, tailored to the individual and their circumstances. Any new trials should be properly designed and conducted, with special attention to reducing loss to follow-up. Individual participant data meta-analysis may help to identify the most effective components of SM interventions.Study registrationThis study is registered as PROSPERO CRD42011001588.FundingThe National Institute for Health Research Health Technology Assessment programme.

BackgroundChronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease characterised by non-reversible airflow obstruction. Exacerbations are a key cause of morbidity and mortality and place a considerable burden on health-care systems. While there is evidence that patients benefit from non-invasive ventilation (NIV) in hospital during an acute exacerbation, evidence supporting home use for more stable COPD patients is limited. In the UK, domiciliary NIV is considered on health economic grounds in patients after three hospital admissions for acute hypercapnic respiratory failure.ObjectiveTo assess the clinical effectiveness and cost-effectiveness of domiciliary NIV by systematic review and economic evaluation.Data sourcesBibliographic databases, conference proceedings and ongoing trial registries up to September 2014.MethodsStandard systematic review methods were used for identifying relevant clinical effectiveness and cost-effectiveness studies assessing NIV compared with usual care or comparing different types of NIV. Risk of bias was assessed using Cochrane guidelines and relevant economic checklists. Results for primary effectiveness outcomes (mortality, hospitalisations, exacerbations and quality of life) were presented, where possible, in forest plots. A speculative Markov decision model was developed to compare the cost-effectiveness of domiciliary NIV with usual care from a UK perspective for post-hospital and more stable populations separately.ResultsThirty-one controlled effectiveness studies were identified, which report a variety of outcomes. For stable patients, a modest volume of evidence found no benefit from domiciliary NIV for survival and some non-significant beneficial trends for hospitalisations and quality of life. For post-hospital patients, no benefit from NIV could be shown in terms of survival (from randomised controlled trials) and findings for hospital admissions were inconsistent and based on limited evidence. No conclusions could be drawn regarding potential benefit from different types of NIV. No cost-effectiveness studies of domiciliary NIV were identified. Economic modelling suggested that NIV may be cost-effective in a stable population at a threshold of £30,000 per quality-adjusted life-year (QALY) gained (incremental cost-effectiveness ratio £28,162), but this is associated with uncertainty. In the case of the post-hospital population, results for three separate base cases ranged from usual care dominating to NIV being cost-effective, with an incremental cost-effectiveness ratio of less than £10,000 per QALY gained. All estimates were sensitive to effectiveness estimates, length of benefit from NIV (currently unknown) and some costs. Modelling suggested that reductions in the rate of hospital admissions per patient per year of 24% and 15% in the stable and post-hospital populations, respectively, are required for NIV to be cost-effective.LimitationsEvidence on key clinical outcomes remains limited, particularly quality-of-life and long-term (> 2 years) effects. Economic modelling should be viewed as speculative because of uncertainty around effect estimates, baseline risks, length of benefit of NIV and limited quality-of-life/utility data.ConclusionsThe cost-effectiveness of domiciliary NIV remains uncertain and the findings in this report are sensitive to emergent data. Further evidence is required to identify patients most likely to benefit from domiciliary NIV and to establish optimum time points for starting NIV and equipment settings.Future work recommendationsThe results from this report will need to be re-examined in the light of any new trial results, particularly in terms of reducing the uncertainty in the economic model. Any new randomised controlled trials should consider including a sham non-invasive ventilation arm and/or a higher- and lower-pressure arm. Individual participant data analyses may help to determine whether or not there are any patient characteristics or equipment settings that are predictive of a benefit of NIV and to establish optimum time points for starting (and potentially discounting) NIV.Study registrationThis study is registered as PROSPERO CRD42012003286.FundingThe National Institute for Health Research Health Technology Assessment programme.

The flash monitoring system has a modest impact on glucose monitoring costs for the UK NHS for patients with T1DM using intensive insulin. For people requiring frequent tests, flash monitoring may be cost saving, especially when taking into account potential reductions in the rate of severe hypoglycaemia.