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Background: Endovascular abdominal aortic aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA) is less invasive than open surgery, but may be associated with important complications. Patients receiving EVAR require long-term surveillance to detect abnormalities and direct treatments. Computed tomography angiography (CTA) has been the most common imaging modality adopted for EVAR surveillance, but it is associated with repeated radiation exposure and the risk of contrast-related nephropathy. Colour duplex ultrasound (CDU) and, more recently, contrast-enhanced ultrasound (CEU) have been suggested as possible, safer, alternatives to CTA., Objectives: To assess the clinical effectiveness and cost-effectiveness of imaging strategies, using either CDU or CEU alone or in conjunction with plain radiography, compared with CTA for EVAR surveillance., Data Sources: Major electronic databases were searched, including MEDLINE, EMBASE, Science Citation Index, Scopus' Articles-in-Press, Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE) and NHS Economic Evaluation Database from 1996 onwards. We also searched for relevant ongoing studies and conference proceedings. The final searches were undertaken in September 2016., Methods: We conducted a systematic review of randomised controlled trials and cohort studies of patients with AAAs who were receiving surveillance using CTA, CDU and CEU with or without plain radiography. Three reviewers were involved in the study selection, data extraction and risk-of-bias assessment. We developed a Markov model based on five surveillance strategies: (1) annual CTA; (2) annual CDU; (3) annual CEU; (4) CDU together with CTA at 1 year, followed by CDU on an annual basis; and (5) CEU together with CTA at 1 year, followed by CEU on an annual basis. All of these strategies also considered plain radiography on an annual basis., Results: We identified two non-randomised comparative studies and 25 cohort studies of interventions, and nine systematic reviews of diagnostic accuracy. Overall, the proportion of patients who required reintervention ranged from 1.1% (mean follow-up of 24 months) to 23.8% (mean follow-up of 32 months). Reintervention was mainly required for patients with thrombosis and types I-III endoleaks. All-cause mortality ranged from 2.7% (mean follow-up of 24 months) to 42% (mean follow-up of 54.8 months). Aneurysm-related mortality occurred in < 1% of the participants. Strategies based on early and mid-term CTA and/or CDU and long-term CDU surveillance were broadly comparable with those based on a combination of CTA and CDU throughout the follow-up period in terms of clinical complications, reinterventions and mortality. The economic evaluation showed that a CDU-based strategy generated lower expected costs and higher quality-adjusted life-year (QALYs) than a CTA-based strategy and has a 63% probability of being cost-effective at a £30,000 willingness-to-pay-per-QALY threshold. A CEU-based strategy generated more QALYs, but at higher costs, and became cost-effective only for high-risk patient groups., Limitations: Most studies were rated as being at a high or moderate risk of bias. No studies compared CDU with CEU. Substantial clinical heterogeneity precluded a formal synthesis of results. The economic model was hindered by a lack of suitable data., Conclusions: Current surveillance practice is very heterogeneous. CDU may be a safe and cost-effective alternative to CTA, with CTA being reserved for abnormal/inconclusive CDU cases., Future Work: Research is needed to validate the safety of modified, more-targeted surveillance protocols based on the use of CDU and CEU. The role of radiography for surveillance after EVAR requires clarification., Study Registration: This study is registered as PROSPERO CRD42016036475., Funding: The National Institute for Health Research Health Technology Assessment programme., Competing Interests: No competing interests were declared.

Background: Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m 2 ] have an increased risk of comorbidities and psychological, social and economic consequences., Objectives: Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment., Data Sources: Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017)., Review Methods: Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m 2 . Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000-30,000., Results: A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [-20.23 kg, 95% confidence interval (CI) -23.75 to -16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of -4.41 kg (95% CI -5.93 to -2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit., Limitations: Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken., Conclusions: Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends., Future Work: Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions., Study Registration: This study is registered as PROSPERO CRD42016040190., Funding: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate., Competing Interests: Alison Avenell, Clare Robertson and Graeme MacLennan acknowledge funding from the National Institute for Health Research Health Technology Assessment programme for projects outside this work. Paul Aveyard was an investigator on an investigator-initiated trial funded by Cambridge Weight Plan, and has done half a day’s consultancy for Weight Watchers. These activities led to payments to the University of Oxford for his time but no payments to him personally.

Background: Dupuytren's disease is a slowly progressive condition of the hand, characterised by the formation of nodules in the palm that gradually develop into fibrotic cords. Contracture of the cords produces deformities of the fingers. Surgery is recommended for moderate and severe contractures, but complications and/or recurrences are frequent. Collagenase clostridium histolyticum (CCH) has been developed as a minimally invasive alternative to surgery for some patients., Objectives: To assess the clinical effectiveness and cost-effectiveness of collagenase as an alternative to surgery for adults with Dupuytren's contracture with a palpable cord., Data Sources: We searched all major electronic databases from 1990 to February 2014., Review Methods: Randomised controlled trials (RCTs), non-randomised comparative studies and observational studies involving collagenase and/or surgical interventions were considered. Two reviewers independently extracted data and assessed risk of bias of included studies. A de novo Markov model was developed to assess cost-effectiveness of collagenase, percutaneous needle fasciotomy (PNF) and limited fasciectomy (LF). Results were reported as incremental cost per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were undertaken to investigate model and parameter uncertainty., Results: Five RCTs comparing collagenase with placebo (493 participants), three RCTs comparing surgical techniques (334 participants), two non-randomised studies comparing collagenase and surgery (105 participants), five non-randomised comparative studies assessing various surgical procedures (3571 participants) and 15 collagenase case series (3154 participants) were included. Meta-analyses of RCTs assessing CCH versus placebo were performed. Joints randomised to collagenase were more likely to achieve clinical success. Collagenase-treated participants experienced significant reduction in contracture and an increased range of motion compared with placebo-treated participants. Participants treated with collagenase also experienced significantly more adverse events, most of which were mild or moderate. Four serious adverse events were observed in the collagenase group: two tendon ruptures, one pulley rupture and one complex regional pain syndrome. Two tendon ruptures were also reported in two collagenase case series. Non-randomised studies comparing collagenase with surgery produced variable results and were at high risk of bias. Serious adverse events across surgery studies were low. Recurrence rates ranged from 0% (at 90 days) to 100% (at 8 years) for collagenase and from 0% (at 2.7 years for fasciectomy) to 85% (at 5 years for PNF) for surgery. The results of the de novo economic analysis show that PNF was the cheapest treatment option, whereas LF generated the greatest QALY gains. Collagenase was more costly and generated fewer QALYs compared with LF. LF was £1199 more costly and generated an additional 0.11 QALYs in comparison with PNF. The incremental cost-effectiveness ratio was £10,871 per QALY gained. Two subgroup analyses were conducted for a population of patients with moderate and severe disease and up to two joints affected. In both subgroup analyses, collagenase remained dominated., Limitations: The main limitation of the review was the lack of head-to-head RCTs comparing collagenase with surgery and the limited evidence base for estimating the effects of specific surgical procedures (fasciectomy and PNF). Substantial differences across studies further limited the comparability of available evidence. The economic model was derived from a naive indirect comparison and was hindered by a lack of suitable data. In addition, there was considerable uncertainty about the appropriateness of many assumptions and parameters used in the model., Conclusions: Collagenase was significantly better than placebo. There was no evidence that collagenase was clinically better or worse than surgical treatments. LF was the most cost-effective choice to treat moderate to severe contractures, whereas collagenase was not. However, the results of the cost-utility analysis are based on a naive indirect comparison of clinical effectiveness, and a RCT is required to confirm or refute these findings., Study Registration: This study is registered as PROSPERO CRD42013006248., Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others., Objectives: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT., Data Sources: MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources., Review Methods: Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness., Results: The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research., Limitations: The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction., Conclusions: The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes., Study Registration: This study is registered as PROSPERO CRD42012002461., Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Obesity increases the risk of many serious illnesses such as coronary heart disease, type 2 diabetes and osteoarthritis. More men than women are overweight or obese in the UK but men are less likely to perceive their weight as a problem and less likely to engage with weight-loss services., Objective: The aim of this study was to systematically review evidence-based management strategies for treating obesity in men and investigate how to engage men in obesity services by integrating the quantitative, qualitative and health economic evidence base., Data Sources: Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials, the Database of Abstracts of Reviews of Effects and the NHS Economic Evaluation Database were searched from inception to January 2012, with a limited update search in July 2012. Subject-specific websites, reference lists and professional health-care and commercial organisations were also consulted., Review Methods: Six systematic reviews were conducted to consider the clinical effectiveness, cost-effectiveness and qualitative evidence on interventions for treating obesity in men, and men in contrast to women, and the effectiveness of interventions to engage men in their weight reduction. Randomised controlled trials (RCTs) with follow-up data of at least 1 year, or any study design and length of follow-up for UK studies, were included. Qualitative and mixed-method studies linked to RCTs and non-randomised intervention studies, and UK-based, men-only qualitative studies not linked to interventions were included. One reviewer extracted data from the included studies and a second reviewer checked data for omissions or inaccuracies. Two reviewers carried out quality assessment. We undertook meta-analysis of quantitative data and a realist approach to integrating the qualitative and quantitative evidence synthesis., Results: From a total of 12,764 titles reviewed, 33 RCTs with 12 linked reports, 24 non-randomised reports, five economic evaluations with two linked reports, and 22 qualitative studies were included. Men were more likely than women to benefit if physical activity was part of a weight-loss programme. Reducing diets tended to produce more favourable weight loss than physical activity alone (mean weight change after 1 year from a reducing diet compared with an exercise programme -3.2 kg, 95% CI -4.8 kg to -1.6 kg). The type of reducing diet did not affect long-term weight loss. A reducing diet plus physical activity and behaviour change gave the most effective results. Low-fat reducing diets, some with meal replacements, combined with physical activity and behaviour change training gave the most effective long-term weight change in men [-5.2 kg (standard error 0.2 kg) after 4 years]. Such trials may prevent type 2 diabetes in men and improve erectile dysfunction. Although fewer men joined weight-loss programmes, once recruited they were less likely to drop out than women (difference 11%, 95% CI 8% to 14%). The perception of having a health problem (e.g. being defined as obese by a health professional), the impact of weight loss on health problems and desire to improve personal appearance without looking too thin were motivators for weight loss amongst men. The key components differ from those found for women, with men preferring more factual information on how to lose weight and more emphasis on physical activity programmes. Interventions delivered in social settings were preferred to those delivered in health-care settings. Group-based programmes showed benefits by facilitating support for men with similar health problems, and some individual tailoring of advice assisted weight loss in some studies. Generally, men preferred interventions that were individualised, fact-based and flexible, which used business-like language and which included simple to understand information. Preferences for men-only versus mixed-sex weight-loss group programmes were divided. In terms of context, programmes which were cited in a sporting context where participants have a strong sense of affiliation showed low drop out rates and high satisfaction. Although some men preferred weight-loss programmes delivered in an NHS context, the evidence comparing NHS and commercial programmes for men was unclear. The effect of family and friends on participants in weight-loss programmes was inconsistent in the evidence reviewed - benefits were shown in some cases, but the social role of food in maintaining relationships may also act as a barrier to weight loss. Evidence on the economics of managing obesity in men was limited and heterogeneous., Limitations: The main limitations were the limited quantity and quality of the evidence base and narrow outcome reporting, particularly for men from disadvantaged and minority groups. Few of the studies were undertaken in the UK., Conclusions: Weight reduction for men is best achieved and maintained with the combination of a reducing diet, physical activity advice or a physical activity programme, and behaviour change techniques. Tailoring interventions and settings for men may enhance effectiveness, though further research is needed to better understand the influence of context and content. Future studies should include cost-effectiveness analyses in the UK setting., Funding: This project was funded by the NIHR Health Technology Assessment programme.