Economic evaluation of Cytosponge®-trefoil factor 3 for Barrett esophagus: A cost-utility analysis of randomised controlled trial data.

BACKGROUND: Esophageal adenocarcinoma has a very poor prognosis unless detected early. The Cytosponge-trefoil factor 3 (TFF3) is a non-endoscopic test for Barrett esophagus, a precursor of esophageal adenocarcinoma. Randomised controlled trial data from the BEST3 trial has shown that an offer of Cytosponge-TFF3 in the primary care setting in England to individuals on medication for acid reflux increases detection of Barrett esophagus 10-fold over a year compared with standard care. This is an economic evaluation of Cytosponge-TFF3 screening versus usual care using data from the BEST3 trial which took place between 20th March 2017 and 21st March 2019. METHODS: A Markov model with a one-year cycle-length and a lifetime time horizon was created, adapting previous modeling work on Cytosponge screening. The impact of one round of Cytosponge screening was modelled in patients with a median age of 69 years (based on BEST3 trial population). Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted on model parameters. FINDINGS: Per person, one round of Cytosponge-TFF3 screening, including confirmatory endoscopy and treatment, in the intervention arm costed £82 more than usual care and generated an additional 0.015 quality-adjusted life-years (QALYs) at an ICER of £5,500 per QALY gained. Probabilistic sensitivity analysis gave an ICER of £5,405 (95% CI -£6,791 to £17,600). The average QALY gain per person is small because the majority of patients in the model will not develop BE and therefore will have no resulting change in their utility, however the small proportion of patients who are identified with BE dysplasia or cancer derive large benefit. At a willingness-to-pay threshold of £20,000 per QALY, the probability that Cytosponge-TFF3 was cost-effective was over 90%. INTERPRETATION: Using data from a pragmatic randomised trial, one-off Cytosponge-TFF3 screen is cost-effective relative to usual care for patients with gastro-esophageal reflux disease, despite relatively low uptake and an older population in this trial setting than previously modelled. Improving Cytosponge-TFF3 uptake and targeting younger patients is likely to further improve cost-effectiveness

The geography of megatrends affecting European agriculture

A range of intensifying pressures is making the future of European agriculture dynamic and contested. Insights into these pressures are needed to inform debates about the future of the sector. In this study, we use a foresight approach to identify, quantify and map megatrends. Megatrends are long-term driving forces which are observable today and will likely have transformational potential in the future. By mapping these megatrends at the regional scale, we establish a geography of megatrends and detect where they coincide. Four megatrends significant for the future of European agriculture at the regional scale are assessed: Climate change, demographic change, (post-) productivism shifts, and increasingly stringent environmental regulations. The direction and intensity of these megatrends differs between regions, which drives regions into different systemic lock-ins or dynamics. In most regions, megatrends converge to destabilize the current system, forewarning impending systemic changes. While the specific megatrends contributing to this instability differ regionally, this result highlights that many regions are on a dynamic rather than stable trajectory, and the governance challenge is to steer these dynamics towards a desirable future. However, some regions are found to be highly persistent, indicating that megatrends reinforce business as usual, and change needs to be triggered through purposeful governance. In a minority of regions megatrends may drive marginalization as the current system becomes increasingly unviable. We argue that research and policies concerning agricultural sustainability transitions should be cognizant of the regional diversity of European megatrends and the pressures they create

‘To be a woman is to make a plan’: a qualitative study exploring mothers’ experiences of the Child Support Grant in supporting children’s diets and nutrition in South Africa

Food security and good nutrition are key determinants of child well-being. There is strong evidence that cash transfers such as South Africa’s Child Support Grant (CSG) have the potential to help address some of the underlying drivers of food insecurity and malnutrition by providing income to caregivers in poor households, but it is unclear how precisely they work to affect child well-being and nutrition. We present results from a qualitative study conducted to explore the role of the CSG in food security and child well-being in poor households in an urban and a rural setting in South Africa

Developing context-specific frameworks for integrated sustainability assessment of agricultural intensity change: An application for Europe

Agriculture plays a central role in achieving most Sustainable Development Goals (SDGs). Sustainable intensi- fication (SI) of agriculture has been proposed as a promising concept for safeguarding global food security, while simultaneously protecting the environment and promoting good quality of life. However, SI often leads to context-specific sustainability trade-offs. Operationalising SI thus needs to be supported by transparent sus- tainability assessments. In this article, we propose a general systematic approach to developing context-specific frameworks for integrated sustainability assessment of agricultural intensity change. Firstly, we specify a comprehensive system representation for analysing how changes in agricultural intensity lead to a multitude of sustainability outcomes affecting different societal groups across geographical scales. We then introduce a procedure for identifying the attributes that are relevant for assessment within particular contexts, and respective indicator metrics. Finally, we illustrate the proposed approach by developing an assessment framework for evaluating a wide range of intensification pathways in Europe. The application of the approach revealed pro- cesses and effects that are relevant for the European context but are rarely considered in SI assessments. These include farmers’ health, workers’ living conditions, cultural heritage and sense of place of rural communities, animal welfare, impacts on sectors not directly related to agriculture (e.g., tourism), shrinking and ageing of rural population and consumers’ health. The proposed approach addresses important gaps in SI assessments, and thus represents an important step forward in defining transparent procedures for sustainability assessments that can stimulate an informed debate about the operationalisation of SI and its contribution towards achieving SDGs

Farmer surveys in Europe suggest that specialized, intensive farms were more likely to perceive negative impacts from COVID-19.

It has been shown that the COVID-19 pandemic affected some agricultural systems more than others, and even within geographic regions, not all farms were affected to the same extent. To build resilience of agricultural systems to future shocks, it is key to understand which farms were affected and why. In this study, we examined farmers' perceived robustness to COVID-19, a key resilience capacity. We conducted standardized farmer interviews (n = 257) in 15 case study areas across Europe, covering a large range of socio-ecological contexts and farm types. Interviews targeted perceived livelihood impacts of the COVID-19 pandemic on productivity, sales, price, labor availability, and supply chains in 2020, as well as farm(er) characteristics and farm management. Our study corroborates earlier evidence that most farms were not or only slightly affected by the first wave(s) of the pandemic in 2020, and that impacts varied widely by study region. However, a significant minority of farmers across Europe reported that the pandemic was "the worst crisis in a lifetime" (3%) or "the worst crisis in a decade" (7%). Statistical analysis showed that more specialized and intensive farms were more likely to have perceived negative impacts. From a societal perspective, this suggests that highly specialized, intensive farms face higher vulnerability to shocks that affect regional to global supply chains. Supporting farmers in the diversification of their production systems while decreasing dependence on service suppliers and supply chain actors may increase their robustness to future disruptions. Supplementary Information The online version contains supplementary material available at 10.1007/s13593-022-00820-5

Enhanced feedback interventions to promote evidence-based blood transfusion guidance and reduce unnecessary use of blood components:The AFFINITIE research programme including two cluster factorial RCTs

Background: Blood transfusion is a common but costly treatment. Repeated national audits in the UK suggest that up to one-fifth of transfusions are unnecessary when judged against recommendations for good clinical practice. Audit and feedback seeks to improve patient care and outcomes by comparing clinical care against explicit standards. It is widely used internationally in quality improvement. Audit and feedback generally has modest but variable effects on patient care. A considerable scope exists to improve the impact that audit and feedback has, particularly through head-to-head trials comparing different ways of delivering feedback. Objectives: The AFFINITIE (Development & Evaluation of Audit and Feedback INterventions to Increase evidence-based Transfusion practIcE) programme aimed to design and evaluate enhanced feedback interventions, within a national blood transfusion audit programme, to promote evidence-based guidance and reduce the unnecessary use of blood components. We developed, piloted and refined two feedback interventions, ‘enhanced content’ and ‘enhanced follow-on’ (workstream 1), evaluated the effectiveness and cost-effectiveness of the two feedback interventions compared with standard feedback practice (workstream 2), examined intervention fidelity and contextual influences (workstream 3) and developed general implementation recommendations and tools for other audit and feedback programmes (workstream 4). Design: Interviews, observations and documentary analysis in four purposively sampled hospitals explored contemporary practice and opportunities for strengthening feedback. We developed two interventions: ‘enhanced content’, to improve the clarity and utility of feedback reports, and ‘enhanced follow-on’, to help hospital staff with action-planning (workstream 1). We conducted two linked 2 × 2 factorial cross-sectional cluster-randomised trials within transfusion audits for major surgery and haematological oncology, respectively (workstream 2). We randomised hospital clusters (the organisational level at which hospital transfusion teams operate) to enhanced or standard content or enhanced or standard follow-on. Outcome assessment was masked to assignment. Decision-analytic modelling evaluated the costs, benefits and cost-effectiveness of the feedback interventions in both trials from the perspective of the NHS. A parallel process evaluation used semistructured interviews, documentary analyses and web analytics to assess the fidelity of delivery, receipt and enactment and to identify contextual influences (workstream 3). We explored ways of improving the impact of national audits with their representatives (workstream 4). Setting and participants: All NHS hospital trusts and health boards participating in the National Comparative Audit of Blood Transfusions were invited to take part. Among 189 hospital trusts and health boards screened, 152 hospital clusters participated in the surgical audit. Among 187 hospital trusts and health boards screened, 141 hospital clusters participated in the haematology audit. Interventions: ‘Enhanced content’ aimed to ensure that the content and format of feedback reports were consistent with behaviour change theory and evidence. ‘Enhanced follow-on’ comprised a web-based toolkit and telephone support to facilitate local dissemination, planning and response to feedback. Main outcome measures: Proportions of acceptable transfusions, based on existing evidence and guidance and algorithmically derived from national audit data. Data sources: Trial primary outcomes were derived from manually collected, patient-level audit data. Secondary outcomes included routinely collected data for blood transfusion. Results: With regard to the transfusions in the major surgery audit, 135 (89%) hospital clusters participated from 152 invited. We randomised 69 and 66 clusters to enhanced and standard content, respectively, and 68 and 67 clusters to enhanced and standard follow-on, respectively. We analysed a total of 2222 patient outcomes at 12 months in 54 and 58 (enhanced and standard content, respectively) and 54 and 58 (enhanced and standard follow-on, respectively) hospital clusters. With regard to the haematology audit, 134 hospital clusters (95%) participated from 141 invited. We randomised 66 and 68 clusters to enhanced and standard content, respectively, and 67 clusters to both enhanced and standard follow-on. We analysed a total of 3859 patient outcomes at 12 months in 61 and 61 (enhanced and standard content, respectively) and 63 and 59 (enhanced and standard follow-on) hospital clusters. We found no effect of either of the enhanced feedback interventions in either trial across all outcomes. Incremental enhanced intervention costs ranged from £18 to £248 per site. The enhanced feedback interventions were dominated by the standard intervention in cost-effectiveness analyses. The interventions were delivered as designed and intended, but subsequent local engagement was low. Although the enhancements were generally acceptable, doubts about the credibility of the blood transfusion audits undermined the case for change. Limitations: Limitations included the number of participating clusters; loss to follow-up of trial clusters, reducing statistical power and validity; incomplete audit and cost data contributing to outcome measures; participant self-selection; reporting; missing data related to additional staff activity generated in response to receiving feedback; and recall biases in the process evaluation interviews. Conclusions: The enhanced feedback interventions were acceptable to recipients but were more costly and no more effective than standard feedback in reducing unnecessary use of blood components, and, therefore, should not be recommended on economic grounds. Future work: We have demonstrated the feasibility of embedding ambitious large-scale rigorous research within national audit programmes. Further head-to-head comparisons of different feedback interventions are needed in these programmes to identify cost-effective ways of increasing the impact of the interventions

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Meta-analyses reveal the importance of socio-psychological factors for farmers’ adoption of sustainable agricultural practices

Agricultural systems support societies in various ways but also cause substantial sustainability challenges. Sustainable agricultural practices are key to achieving sustainability targets, yet we lack generalizable knowledge on why farmers apply such practices. Here, we quantified the relationship between farmers’ adoption of sustainable agricultural practices and their underlying motivational factors. Based on a systematic review, we meta-analyzed 14 motivational factors from 225 studies reporting 522 effect sizes, representing 327,778 farmers from 23 European countries. We found (1) substantially stronger positive effects for general attitude, intention and perceived usefulness compared with economic outcomes and environmental awareness, (2) dissonance between intention and actual behavior, and (3) geographic, thematic, and effort-effect bias in literature. Stimulating the adoption of sustainable agricultural practices hence requires reconsidering the currently strong emphasis on economic factors in favor of a wider set of motivational factors, especially by addressing socio-psychological factors via transparency, communication, and training