Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD. We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83–2.76, p < 0.001, I² 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m²) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12–1.28, p < 0.001, I² 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome. In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease. PROSPERO CRD42018115459.

Objectives To determine the diagnostic accuracy of duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography, alone or in combination, for the assessment of lower limb peripheral arterial disease; to evaluate the impact of these assessment methods on management of patients and outcomes; and to evaluate the evidence regarding attitudes of patients to these technologies and summarise available data on adverse events. Design Systematic review. Methods Searches of 11 electronic databases (to April 2005), six journals, and reference lists of included papers for relevant studies. Two reviewers independently selected studies, extracted data, and assessed quality. Diagnostic accuracy studies were assessed for quality with the QUADAS checklist. Results 107 studies met the inclusion criteria; 58 studies provided data on diagnostic accuracy, one on outcomes in patients, four on attitudes of patients, and 44 on adverse events. Quality assessment highlighted limitations in the methods and quality of reporting. Most of the included studies reported results by arterial segment, rather than by limb or by patient, which does not account for the clustering of segments within patients, so specificities may be overstated. For the detection of stenosis of 50% or more in a lower limb vessel, contrast enhanced magnetic resonance angiography had the highest diagnostic accuracy with a median sensitivity of 95% (range 92-99.5%) and median specificity of 97% (64-99%). The results were 91% (89-99%) and 91% (83-97%) for computed tomography angiography and 88% (80-98%) and 96% (89-99%) for duplex ultrasonography. A controlled trial reported no significant differences in outcomes in patients after treatment plans based on duplex ultrasonography alone or conventional contrast angiography alone, though in 22% of patients supplementary contrast angiography was needed to form a treatment plan. The limited evidence available suggested that patients preferred magnetic resonance angiography (with or without contrast) to contrast angiography, with half expressing no preference between magnetic resonance angiography or duplex ultrasonography (among patients with no contraindications for magnetic resonance angiography, such as claustrophobia). Where data on adverse events were available, magnetic resonance angiography was associated with the highest proportion of adverse events, but these were mild. The most severe adverse events, although rare, were mainly associated with contrast angiography. Conclusions Contrast enhanced magnetic resonance angiography seems to be more specific than computed tomography angiography (that is, better at ruling out stenosis over 50%) and more sensitive than duplex ultrasonography (that is, better at ruling in stenosis over 50%) and was generally preferred by patients over contrast angiography. Computed tomography angiography was also preferred by patients over contrast angiography; no data on patients' preference between duplex ultrasonography and contrast angiography were available. Where available, contrast enhanced magnetic resonance angiography might be a viable alternative to contrast angiography.

Objectives To compare the effectiveness and safety of surgical interventions for women with stress urinary incontinence. Design Systematic review and network meta-analysis. Eligibility criteria for selecting studies Randomised controlled trials evaluating surgical interventions for the treatment of stress urinary incontinence in women. Methods Identification of relevant randomised controlled trials from Cochrane reviews and the Cochrane Incontinence Specialised Register (searched May 2017), which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Medline In-Process, Medline Epub Ahead of Print, CINAHL, ClinicalTrials.gov, and WHO ICTRP. The reference lists of relevant articles were also searched. Primary outcomes were “cure” and “improvement” at 12 months, analysed by means of network meta-analyses, with results presented as the surface under the cumulative ranking curve (SUCRA). Adverse events were analysed using pairwise meta-analyses. Risk of bias was assessed using the Cochrane risk of bias tool. The quality of evidence for network meta-analysis was assessed using the GRADE approach. Results 175 randomised controlled trials assessing a total of 21 598 women were included. Most studies had high or unclear risk across all risk of bias domains. Network meta-analyses were based on data from 105 trials that reported cure and 120 trials that reported improvement of incontinence symptoms. Results showed that the interventions with highest cure rates were traditional sling, retropubic midurethral sling (MUS), open colposuspension, and transobturator MUS, with rankings of 89.4%, 89.1%, 76.7%, and 64.1%, respectively. Compared with retropubic MUS, the odds ratio of cure for traditional sling was 1.06 (95% credible interval 0.62 to 1.85), for open colposuspension was 0.85 (0.54 to 1.33), and for transobtrurator MUS was 0.74 (0.59 to 0.92). Women were also more likely to experience an improvement in their incontinence symptoms after receiving retropubic MUS or transobturator MUS compared with other surgical procedures. In particular, compared with retropubic MUS, the odds ratio of improvement for transobturator MUS was 0.76 (95% credible interval 0.59 to 0.98), for traditional sling was 0.69 (0.39 to 1.26), and for open colposuspension was 0.65 (0.41 to 1.02). Quality of evidence was moderate for retropubic MUS versus transobturator MUS and low or very low for retropubic MUS versus the other two interventions. Data on adverse events were available mainly for mesh procedures, indicating a higher rate of repeat surgery and groin pain but a lower rate of suprapubic pain, vascular complications, bladder or urethral perforation, and voiding difficulties after transobturator MUS compared with retropubic MUS. Data on adverse events for non-MUS procedures were sparse and showed wide confidence intervals. Long term data were limited. Conclusions Retropubic MUS, transobturator MUS, traditional sling, and open colposuspension are more effective than other procedures for stress urinary incontinence in the short to medium term. Data on long term effectiveness and adverse events are, however, limited, especially around the comparative adverse events profiles of MUS and non-MUS procedures. A better understanding of complications after surgery for stress urinary incontinence is imperative. Systematic review registration PROSPERO CRD42016049339.

Background: Urinary incontinence in women is a distressing condition that restricts quality of life and results in a large economic burden to both the NHS and women themselves.Objective: To evaluate the clinical effectiveness, safety and cost-effectiveness of surgical treatment for stress urinary incontinence (SUI) in women and explore women’s preferences.Design: An evidence synthesis, a discrete choice experiment (DCE) and an economic decision model, with a value-of-information (VOI) analysis. Nine surgical interventions were compared. Previous Cochrane reviews for each were identified and updated to include additional studies. Systematic review methods were applied. The outcomes of interest were ‘cure’ and ‘improvement’. Both a pairwise and a network meta-analysis (NMA) were conducted for all available surgical comparisons. A DCE was undertaken to assess the preferences of women for treatment outcomes. An economic model assessed the cost-effectiveness of alternative surgeries and a VOI analysis was undertaken.Results: Data from 175 studies were included in the effectiveness review. The majority of included studies were rated as being at high or unclear risk of bias across all risk-of-bias domains. The NMA, which included 120 studies that reported data on ‘cure’ or ‘improvement’, showed that retropubic mid-urethral sling (MUS), transobturator MUS, traditional sling and open colposuspension were more effective than other surgical procedures for both primary outcomes. The results for other interventions were variable. In general, rate of tape and mesh exposure was higher after transobturator MUS than after retropubic MUS or single-incision sling, whereas the rate of tape or mesh erosion/extrusion was similar between transobturator MUS and retropubic MUS. The results of the DCE, in which 789 women completed an anonymous online questionnaire, indicate that women tend to prefer surgical treatments associated with no pain or mild chronic pain and shorter length of hospital stay as well as those treatments that have a smaller risk for urinary symptoms to reoccur after surgery. The cost-effectiveness results suggest that, over a lifetime, retropubic MUS is, on average, the least costly and most effective surgery. However, the high level of uncertainty makes robust estimates difficult to ascertain. The VOI analysis highlighted that further research around the incidence rates of complications would be of most value.Limitations: Overall, the quality of the clinical evidence was low, with limited data available for the assessment of complications. Furthermore, there is a lack of robust evidence and significant uncertainty around some parameters in the economic modelling.Conclusions: To our knowledge, this is the most comprehensive assessment of published evidence for the treatment of SUI. There is some evidence that retropubic MUS, transobturator MUS and traditional sling are effective in the short to medium term and that retropubic MUS is cost-effective in the medium to long term. The VOI analysis highlights the value of further research to reduce the uncertainty around the incidence rates of complications. There is a need to obtain robust clinical data in future work, particularly around long-term complication rates.Study registration: This study is registered as PROSPERO CRD42016049339.Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: The 2020 COVID-19 pandemic prompted the rapid implementation of new and existing digital technologies to facilitate access to health and care services during physical distancing. Older people may be disadvantaged in that regard if they are unable to use or have access to smartphones, tablets, computers, or other technologies. Objective: In this study, we synthesized evidence on the impact of digital technologies on older adults’ access to health and social services. Methods: We conducted an umbrella review of systematic reviews published from January 2000 to October 2019 using comprehensive searches of 6 databases. We looked for reviews in a population of adults aged ≥65 years in any setting, reporting outcomes related to the impact of technologies on access to health and social care services. Results: A total of 7 systematic reviews met the inclusion criteria, providing data from 77 randomized controlled trials and 50 observational studies. All of them synthesized findings from low-quality primary studies, 2 of which used robust review methods. Most of the reviews focused on digital technologies to facilitate remote delivery of care, including consultations and therapy. No studies examined technologies used for first contact access to care, such as online appointment scheduling. Overall, we found no reviews of technology to facilitate first contact access to health and social care such as online appointment booking systems for older populations. Conclusions: The impact of digital technologies on equitable access to services for older people is unclear. Research is urgently needed in order to understand the positive and negative consequences of digital technologies on health care access and to identify the groups most vulnerable to exclusion.

National guidance on preventing type 2 diabetes mellitus (T2DM) in the UK recommends low-intensity lifestyle interventions for individuals with intermediate categories of hyperglycaemia defined in terms of impaired fasting glucose (IFG) or ‘at-risk’ levels of HbA1c. In a recent systematic review of economic evaluations of such interventions, most studies had evaluated intensive trial-based lifestyle programmes in participants with impaired glucose tolerance (IGT). This study examines the costs and effects of different intensity lifestyle programmes and metformin in participants with different categories of intermediate hyperglycaemia. We developed a decision tree and Markov model (50-year horizon) to compare four approaches, namely (1) a low-intensity lifestyle programme based on current NICE guidance, (2) a high-intensity lifestyle programme based on the US Diabetes Prevention Program, (3) metformin, and (4) no intervention, modelled for three different types of intermediate hyperglycaemia (IFG, IGT and HbA1c). A health system perspective was adopted and incremental analysis undertaken at an individual and population-wide level, taking England as a case study. Low-intensity lifestyle programmes were the most cost-effective (£44/QALY, £195/QALY and £186/QALY compared to no intervention in IGT, IFG and HbA1c, respectively). Intensive lifestyle interventions were also cost-effective compared to no intervention (£2775/QALY, £6820/QALY and £7376/QALY, respectively, in IGT, IFG and HbA1c). Metformin was cost-effective relative to no intervention (£5224/QALY, £6842/QALY and £372/QALY in IGT, IFG and HbA1c, respectively), but was only cost-effective relative to other treatments in participants identified with HbA1c. At a willingness-to-pay threshold of £20,000/QALY, low- and high-intensity lifestyle programmes were cost-effective 98%, 99% and 98% and 81%, 81% and 71% of the time in IGT, IFG and HbA1c, respectively. An England-wide programme for 50–59 year olds could reduce T2DM incidence by < 3.5% over 50 years and would cost 0.2–5.2% of the current diabetes budget for 2–9 years. This analysis suggests that current English national policy of low-intensity lifestyle programmes in participants with IFG or HbA1c will be cost-effective and have the most favourable budget impact, but will prevent only a fraction of cases of T2DM. Additional approaches to prevention need to be investigated urgently.